Effective treatment of liver metastases with photodynamic therapy, using the second-generation photosensitizer meta tetra(hydroxyphenyl)chlorin (mTHPC), in a rat model

The only curative treatment for patients with liver metastases to date is s urgery, but few patients are suitable candidates for hepatic resection. The majority of patients will have to rely on other treatment modalities for p alliation. Photodynamic therapy (PDT) could be a selective, minimally invas ive treatment for patients with liver metastases. We studied PDT in an impl anted colon carcinoma in the liver of Wag/Rij rats, using the photosensitiz er meta-tetra(hydroxyphenyl)chlorin (mTHPC), mTHPC tissue kinetics were stu died using ex vivo extractions and in vivo fluorescence measurements. Both methods showed that mTHPC kinetics were different for liver and tumour tiss ue. After initial high levels at 4 h after administration (0.1 and 0.3 mg k g(-1)) mTHPC in liver tissue decreased rapidly in time. In tumour tissue no decrease in photosensitizer levels occurred, with mTHPC remaining high up to 48 h after administration. Both concentration data and fluorescence data showed an increase in tumour to liver ratios of up to 6.3 and 5.0 respecti vely. Illumination with 652 nm (15 J) resulted in extensive damage to tumou r tissue, with necrosis of up to 13 mm in diameter. Damage to normal liver tissue was mild and transient as serum aspartate aminotransferase and alani ne aminotransferase levels normalized within a week after PDT treatment. Lo ng-term effects of mTHPC-PDT were studied on day 28 after treatment. Regard less of drug dose and drug-light interval, PDT with mTHPC resulted in compl ete tumour remission in 27 out of 31 treated animals (87%), with only four animals in which tumour regrowth was observed. Non-responding tumours prove d to be significantly larger (P < 0.001) in size before PDT treatment. This study demonstrates that mTHPC is retained in an intrahepatic tumour and th at mTHPC-PDT is capable of inducing complete tumour remission of liver tumo urs. (C) 1999 Cancer Research Campaign.